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BACKGROUND: Countries are currently seeking evidence-informed policy options to address antimicrobial resistance (AMR). While rigorous evaluations of AMR interventions are the ideal, they are far from the current reality. Additionally, poor reporting and documentation of AMR interventions impede efforts to use evidence to inform future evaluations and policy interventions. OBJECTIVES: To critically evaluate reporting quality gaps in AMR intervention research. METHODS: To evaluate the reporting quality of studies, we conducted a descriptive synthesis and comparative analysis of studies that were included in a recent systematic review of government policy interventions aiming to reduce human antimicrobial use. Reporting quality was assessed using the SQUIRE 2.0 checklist of 18 items for reporting system-level interventions to improve healthcare. Two reviewers independently applied the checklist to 66 studies identified in the systematic review. RESULTS: None of the studies included complete information on all 18 SQUIRE items (median score = 10, IQR = 8-11). Reporting quality varied across SQUIRE items, with 3% to 100% of studies reporting the recommended information for each SQUIRE item. Only 20% of studies reported the elements of the intervention in sufficient detail for replication and only 24% reported the mechanism through which the intervention was expected to work. CONCLUSIONS: Gaps in the reporting of impact evaluations pose challenges for interpreting and replicating study results. Failure to improve reporting practice of policy evaluations is likely to impede efforts to tackle the growing health, social and economic threats posed by AMR.
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Antibacterianos , Anti-Infecciosos , Antibacterianos/uso terapêutico , Lista de Checagem , HumanosRESUMO
Antimicrobial resistance (AMR) has the potential to threaten tens of millions of lives and poses major global economic and development challenges. As the AMR threat grows, it is increasingly important to strengthen the scientific evidence base on AMR policy interventions, to learn from existing policies and programmes, and to integrate scientific evidence into the global AMR response.While rigorous evaluations of AMR policy interventions are the ideal, they are far from the current reality. To strengthen this evidence base, we describe a framework for planning, conducting and disseminating research on AMR policy interventions. The framework identifies challenges in AMR research, areas for enhanced coordination and cooperation with decision-makers, and best practices in the design of impact evaluations for AMR policies.This framework offers a path forward, enabling increased local and global cooperation, and overcoming common limitations in existing research on AMR policy interventions.
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Gestão de Antimicrobianos , Farmacorresistência Bacteriana , Pesquisa sobre Serviços de Saúde , Antibacterianos/uso terapêutico , Política de Saúde , HumanosRESUMO
BACKGROUND: Shared decision-making (SDM) is a key priority to improve patient-centred care, and can play an important role in helping patients decide whether to undergo total joint arthroplasty (TJA). Patient decision aids can support SDM; however, they may incur an upfront cost. We aimed to estimate the health and economic effects of patient decision aids for TJA. METHODS: A cost-effectiveness analysis of a randomised controlled trial (RCT) with 2-year follow-up. 343 patients were recruited from two orthopedic screening clinics in Ottawa, Canada. Patients were randomized to either a patient decision aid plus surgeon preference report (decision aid) or usual care. Primary outcomes were costs (in 2014 CAD$), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Costs were calculated by multiplying self-reported resource use by unit costs. QALYs were calculated by mapping the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to EuroQol 5-Dimension (EQ-5D) health utilities. Costs and QALYs were discounted at 5%. Multiple imputation was used to handle missing data, and bootstrapping was used to estimate uncertainty. RESULTS: The sample comprised 167 intervention and 167 control group patients. The decision aid arm had fewer surgeries over the 2-year period thereby incurring a negative incremental cost of -$560 (95% CI: -$1358 to $426) per patient while providing 0.05 (95% CI: -0.04 to 0.13) additional QALYs per patient. Consequently, the decision aid arm was dominant. CONCLUSION: The use of a patient decision aid was associated with fewer health care costs, while producing similar health outcomes. CLINICAL TRIAL REGISTRATION NUMBER: CT00911638 (clinicaltrials.gov).
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Artroplastia de Quadril/psicologia , Artroplastia do Joelho/psicologia , Técnicas de Apoio para a Decisão , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Participação do Paciente/métodos , Idoso , Análise Custo-Benefício , Tomada de Decisões , Feminino , Seguimentos , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Participação do Paciente/economia , Assistência Centrada no Paciente/economia , Assistência Centrada no Paciente/métodos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).
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Artroplastia de Quadril , Artroplastia do Joelho , Tomada de Decisões , Técnicas de Apoio para a Decisão , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Conflito Psicológico , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Participação do Paciente , Modelos de Riscos Proporcionais , Método Simples-Cego , Fatores de TempoRESUMO
Justifying sample size for a pilot trial is a reporting requirement, but few pilot trials report a clear rationale for their chosen sample size. Unlike full-scale trials, pilot trials should not be designed to test effectiveness, and so, conventional sample size justification approaches do not apply. Rather, pilot trials typically specify a range of primary and secondary feasibility objectives. Often, these objectives relate to estimation of parameters that inform the sample size justification for the full-scale trial, many of which are binary. These binary outcomes are referred to as "feasibility outcomes" and include expected prevalence of the primary trial outcome, primary outcome availability, or recruitment or retention proportions.For pilot cluster trials, sample size calculations depend on the number of clusters, the cluster sizes, the anticipated intra-cluster correlation coefficient for the feasibility outcome and the anticipated proportion for that outcome. Of key importance is the intra-cluster correlation coefficient for the feasibility outcome. It has been suggested that correlations for feasibility outcomes are larger than for clinical outcomes measuring effectiveness. Yet, there is a dearth of information on realised values for these correlations.In this tutorial, we demonstrate how to justify sample size in external pilot cluster trials where the objective is to estimate a binary feasibility outcome. We provide sample size calculation formulae for a variety of scenarios, make available an R Shiny app for implementation, and compile a report of intra-cluster correlations for feasibility outcomes from a convenience sample. We demonstrate that unless correlations are very low, external pilot cluster trials can be made more efficient by including more clusters and fewer observations per cluster.
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BACKGROUND: Self-administered cognitive behavior therapy (SCBT) has been shown to be an effective alternative to therapist-delivered treatment for panic disorder (PD). However, it is unknown whether combining SCBT and antidepressants can improve treatment. This trial evaluated the efficacy of SCBT and sertraline, alone or in combination, in PD. METHOD: Patients (n=251) were randomized to 12 weeks of either placebo drug, placebo drug plus SCBT, sertraline, or sertraline plus SCBT. Those who improved after 12 weeks of acute treatment received treatment for an additional 12 weeks. Outcome measures included core PD symptoms (panic attacks, anticipatory anxiety, agoraphobic avoidance), dysfunctional cognitions (fear of bodily sensations, agoraphobic cognitions), disability, and clinical global impression of severity and improvement. Efficacy data were analyzed using general and generalized linear mixed models. RESULTS: Primary analyses of trends over time revealed that sertraline/SCBT produced a significantly greater rate of decline in fear of bodily sensations compared to sertraline, placebo/SCBT and placebo. Trends in other outcomes were not significantly different over time. Secondary analyses of mean scores at week 12 revealed that sertraline/SCBT fared better on several outcomes than placebo, with improvement being maintained at the end of continuation treatment. Outcome did not differ between placebo and either sertraline monotherapy or placebo/SCBT. Moreover, few differences emerged between the active interventions. CONCLUSIONS: This trial suggests that sertraline combined with SCBT may be an effective treatment for PD. The study could not confirm the efficacy of sertraline monotherapy or SCBT without concomitant medication or therapist assistance in the treatment of PD.
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Terapia Cognitivo-Comportamental , Transtorno de Pânico/terapia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Autocuidado , Sertralina/uso terapêutico , Adulto , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Funções Verossimilhança , Modelos Lineares , MasculinoRESUMO
Clinical prediction models are developed with the ultimate aim of improving patient outcomes, and are often turned into prediction rules (e.g. classifying people as low/high risk using cut-points of predicted risk) at some point during the development stage. Prediction rules often have reasonable ability to either rule-in or rule-out disease (or another event), but rarely both. When a prediction model is intended to be used as a prediction rule, conveying its performance using the C-statistic, the most commonly reported model performance measure, does not provide information on the magnitude of the trade-offs. Yet, it is important that these trade-offs are clear, for example, to health professionals who might implement the prediction rule. This can be viewed as a form of knowledge translation. When communicating information on trade-offs to patients and the public there is a large body of evidence that indicates natural frequencies are most easily understood, and one particularly well-received way of depicting the natural frequency information is to use population diagrams. There is also evidence that health professionals benefit from information presented in this way.Here we illustrate how the implications of the trade-offs associated with prediction rules can be more readily appreciated when using natural frequencies. We recommend that the reporting of the performance of prediction rules should (1) present information using natural frequencies across a range of cut-points to inform the choice of plausible cut-points and (2) when the prediction rule is recommended for clinical use at a particular cut-point the implications of the trade-offs are communicated using population diagrams. Using two existing prediction rules, we illustrate how these methods offer a means of effectively and transparently communicating essential information about trade-offs associated with prediction rules.
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Background: In Ontario, an online audit and feedback tool that provides primary care physicians with detailed information about patients who are overdue for cancer screening is underused. In the present study, we aimed to examine the effect of messages operationalizing 3 behaviour change techniques on access to the audit and feedback tool and on cancer screening rates. Methods: During May-September 2017, a pragmatic 2×2×2 factorial experiment tested 3 behaviour change techniques: anticipated regret, material incentive, and problem-solving. Outcomes were assessed using routinely collected administrative data. A qualitative process evaluation explored how and why the e-mail messages did or did not support Screening Activity Report access. Results: Of 5449 primary care physicians randomly allocated to 1 of 8 e-mail messages, fewer than half opened the messages and fewer than 1 in 10 clicked through the messages. Messages with problem-solving content were associated with a 12.9% relative reduction in access to the tool (risk ratio: 0.871; 95% confidence interval: 0.791 to 0.958; p = 0.005), but a 0.3% increase in cervical cancer screening (rate ratio: 1.003; 95% confidence interval: 1.001 to 1.006; p = 0.003). If true, that association would represent 7568 more patients being screened. No other significant effects were observed. Conclusions: For audit and feedback to work, recipients must engage with the data; for e-mail messages to prompt activity, recipients must open and review the message content. This large factorial experiment demonstrated that small changes in the content of such e-mail messages might influence clinical behaviour. Future research should focus on strategies to make cancer screening more user-centred.
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Detecção Precoce de Câncer , Correio Eletrônico , Programas de Rastreamento , Médicos , Atenção Primária à Saúde , Comportamento , Feminino , Feedback Formativo , Humanos , Masculino , Motivação , Resolução de Problemas , Garantia da Qualidade dos Cuidados de Saúde , Distribuição AleatóriaRESUMO
BACKGROUND: Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. METHODS: An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. RESULTS: A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. CONCLUSION: The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.
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Equidade em Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Consenso , Disparidades nos Níveis de Saúde , Humanos , Justiça Social , Fatores SocioeconômicosRESUMO
OBJECTIVE To assess the clinical effectiveness of a universal screening program compared with a risk factor-based program in reducing the rates of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) among admitted patients at the Ottawa Hospital. DESIGN Quasi-experimental study. SETTING Ottawa Hospital, a multicenter tertiary care facility with 3 main campuses, approximately 47,000 admissions per year, and 1,200 beds. METHODS From January 1, 2006 through December 31, 2007 (24 months), admitted patients underwent risk factor-based MRSA screening. From January 1, 2008 through August 31, 2009 (20 months), all patients admitted underwent universal MRSA screening. To measure the effectiveness of this intervention, segmented regression modeling was used to examine monthly nosocomial MRSA incidence rates per 100,000 patient-days before and during the intervention period. To assess secular trends, nosocomial Clostridium difficile infection, mupirocin prescriptions, and regional MRSA rates were investigated as controls. RESULTS The nosocomial MRSA incidence rate was 46.79 cases per 100,000 patient-days, with no significant differences before and after intervention. The MRSA detection rate per 1,000 admissions increased from 9.8 during risk factor-based screening to 26.2 during universal screening. A total of 644 new nosocomial MRSA cases were observed in 1,448,488 patient-days, 323 during risk factor-based screening and 321 during universal screening. Secular trends in C. difficile infection rates and mupirocin prescriptions remained stable after the intervention whereas population-level MRSA rates decreased. CONCLUSION At Ottawa Hospital, the introduction of universal MRSA admission screening did not significantly affect the rates of nosocomial MRSA compared with risk factor-based screening. Infect. Control Hosp. Epidemiol. 2015;37(1):41-48.
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Clostridioides difficile , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Programas de Rastreamento/métodos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Canadá/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mupirocina/uso terapêutico , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Circulating PCSK9 levels are higher in women than men, in postmenopausal than premenopausal women, and in pregnant than non-pregnant women, suggesting that sex hormones may be related to PCSK9 levels. We have examined the relationship between serum estradiol (E2) and testosterone (T) and PCSK9, and the impact of E2 replacement therapy in women and T replacement and ablation therapy in men on circulating PCSK9. METHODS: We conducted a cross-sectional study to examine the correlation between serum T (in males) and E2 (in females) and serum PCSK9. We also conducted interventional studies to examine the effect of hormonal therapy on serum PCSK9 levels. RESULTS: In men, (1) serum T does not correlate with circulating PCSK9 or with LDLC in the basal state, (2) T replacement therapy does not have any effect on circulating PCSK9, and (3) T ablation therapy has mixed results. In women, (1) E2 correlates inversely with circulating PCSK9 and directly with serum LDLC, but (2) E2 replacement therapy does not have any effect on circulating PCSK9. CONCLUSIONS: We demonstrate differences between men and women in the relationship of their major sex hormones with circulating PCSK9. In men, circulating PCSK9 is not related to or affected by T except for a possible effect during T ablation therapy. In women, E2 is inversely related to circulating PCSK9 but the lack of effect of E2 therapy on circulating PCSK9 suggests that the E2-related differences in PCSK9 levels may be the result of differences in receptor-mediated PCSK9 clearance through E2-induced changes rather than production of PCSK9. The studies were registered with ClinicalTrials.gov NCT00848276.
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Estradiol/sangue , Pró-Proteína Convertases/sangue , Serina Endopeptidases/sangue , Caracteres Sexuais , Testosterona/sangue , Adulto , Estudos de Coortes , Estudos Transversais , Intervenção Médica Precoce/tendências , Terapia de Reposição de Estrogênios/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9 , Testosterona/administração & dosagemRESUMO
BACKGROUND: Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). METHODS/DESIGN: A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. DISCUSSION: This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies.
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Guias como Assunto , Equidade em Saúde/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa , Fatores Etários , Cultura , Humanos , Fatores Sexuais , Fatores SocioeconômicosRESUMO
OBJECTIVES: Serum low density lipoprotein-cholesterol (LDL-C) correlates positively with serum PCSK9 in the general population, consistent with PCSK9 being a determinant of LDL-C levels. Patients with chronic kidney disease (CKD) on hemodialysis (HD) have lower total cholesterol (TC) and LDL-C compared to the general population. Serum PCSK9 and its relationship with serum lipids have not been reported in CKD patients on HD (CKD-HD). METHODS: We measured serum PCSK9 by ELISA and lipid levels in 66 CKD-HD patients and compared them to 178 non-CKD subjects. Since statins increase serum PCSK9 levels, CKD-HD patients were separated into those not on statin therapy (HD-NS, n = 32) and those taking statins (HD-S, n = 34). No control subjects were on statin therapy. RESULTS: Serum PCSK9, TC, LDL-C and HDL-C levels were significantly lower in the CKD-HD group (n = 66) compared to the control group. HD-NS patients showed lower PCSK9, TC and LDL-C levels than control subjects and PCSK9 levels correlated with TC and LDL-C levels (r = 0.35, p = 0.050; r = 0.423, p = 0.0158 respectively) as well as TG levels (r = 0.413, p = 0.0188). In HD-S patients, PCSK9 levels were not significantly different from the non-CKD group. There was no correlation between PCSK9 levels and TC and LDL-C levels in the HD-S group. CONCLUSION: Our data are the first quantitative analysis of serum PCSK9 levels in CKD-HD patients. We show that serum PCSK9 in HD-NS patients is decreased and it retains a positive correlation with LDL-C, suggesting that PCSK9 may remain a significant determinant of LDL-C in CKD-HD subjects. We also show that statin therapy disrupts the correlation between LDL-C and PCSK9 in CKD-HD patients. These data suggest that the regulation of LDL-C by PCSK9 remains intact in CKD-HD patients. PCSK9 may also play a role in the metabolism of triglyceride-rich lipoproteins in CKD-HD patients.
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LDL-Colesterol/sangue , Pró-Proteína Convertases/sangue , Insuficiência Renal Crônica/enzimologia , Serina Endopeptidases/sangue , HDL-Colesterol/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9 , Diálise Renal , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
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Cumarínicos/administração & dosagem , Sistema Enzimático do Citocromo P-450/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Alelos , Hidrocarboneto de Aril Hidroxilases/genética , Estudos de Coortes , Cumarínicos/uso terapêutico , Estudos Transversais , Citocromo P-450 CYP2C9 , Família 4 do Citocromo P450 , Etnicidade , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Viés de Publicação , Fatores Sexuais , Vitamina K Epóxido RedutasesRESUMO
OBJECTIVE: To assess the impact of the 2004 extension of the CONSORT guidelines on the reporting and methodological quality of cluster randomised trials. DESIGN: Methodological review of 300 randomly sampled cluster randomised trials. Two reviewers independently abstracted 14 criteria related to quality of reporting and four methodological criteria specific to cluster randomised trials. We compared manuscripts published before CONSORT (2000-4) with those published after CONSORT (2005-8). We also investigated differences by journal impact factor, type of journal, and trial setting. DATA SOURCES: A validated Medline search strategy. Eligibility criteria for selecting studies Cluster randomised trials published in English language journals, 2000-8. RESULTS: There were significant improvements in five of 14 reporting criteria: identification as cluster randomised; justification for cluster randomisation; reporting whether outcome assessments were blind; reporting the number of clusters randomised; and reporting the number of clusters lost to follow-up. No significant improvements were found in adherence to methodological criteria. Trials conducted in clinical rather than non-clinical settings and studies published in medical journals with higher impact factor or general medical journals were more likely to adhere to recommended reporting and methodological criteria overall, but there was no evidence that improvements after publication of the CONSORT extension for cluster trials were more likely in trials conducted in clinical settings nor in trials published in either general medical journals or in higher impact factor journals. CONCLUSION: The quality of reporting of cluster randomised trials improved in only a few aspects since the publication of the extension of CONSORT for cluster randomised trials, and no improvements at all were observed in essential methodological features. Overall, the adherence to reporting and methodological guidelines for cluster randomised trials remains suboptimal, and further efforts are needed to improve both reporting and methodology.
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Guias como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/normasRESUMO
BACKGROUND: Pharmacogenomic warfarin dosing has been suggested to produce more accurate dosing and an improved patient safety profile; however, very few models have been derived in patients with venous thromboembolism. We sought to develop a new algorithm to predict maintenance dose in a cohort of patients, using clinical variables and genetic polymorphism in CYP2C9, VKORC1, and CYP4F2. METHODS: Patients on a stable maintenance dose of warfarin, with observed dose ranging from 0.6 to 12mg were recruited from a specialized anticoagulation clinic (Ottawa Hospital Thrombosis Clinic) with genotyping and standardized patient interviews being conducted to collect clinical and genomic variables known to impact warfarin dose. Multivariate linear regression was used to develop the model using a stepwise backwards elimination approach. RESULTS: From 249 enrolled patients with a mean clinical maintenance dose of 5.58mg/day, a model with an R(2) of 58% was developed as: Dose=1.85-0.048(Age)+0.041(BMI)+0.05(Height in cm) - 0.73(Less Exercise) - 1.13(2C9*2 Hetero) - 2.09(2C9*2 Homo) - 1.51(2C9*3 Hetero) -1.43(VKORC1 GA) - 2.86(VKORC1 AA) - 1.33(4F2 CC) -1.24(4F2 CT) - 1.46(Angiotensin II Receptor Antagonist) - 0.84(beta-Blockers). Analysis of residual plots revealed that prediction errors were a function of observed maintenance dose with the model tending to predict higher doses than observed in those with low dose requirements and lower doses than observed in those with higher dose requirement. CONCLUSION: Our study confirms the importance of the CYP4F2 polymorphism. Our model may prove useful in clinical practice but further validation studies are required before implementation into clinical practice.